Tumor RNA-transfected dendritic cells and combined therapy with low dose 5-FU induce regression of murine colon cancer

We have recently observed that treatment of colon tumor cells with low concentration of paclitaxel increased the expression of several genes associated with antigen-presenting machinery. Since 5-fluoruracil (5-FU) is the main antineoplastic agent for colon cancer, in this study we aimed to evaluate: a) whether transfection of dendritic cells (DC) with drug-treated tumor cells RNA, enhances the effectiveness of DC-based vaccine; b) if the modulatory effects of vaccine can be observed in vivo, and c) if the combination of DC with low dose chemotherapy schedule improves the antitumor responsiveness.

Murine colon cancer cells (MC-38) were treated with the minimum effective concentration (MEC) of 5-FU and their RNA was used to transfect DC. Then, C57/Bl-6 tumor-bearing mice were treated with DC vaccine. Another group of animals received low doses of chemotherapy schedule and DC vaccine.

Results of 2 independent assays have shown that vaccination with RNA-transfected DC delayed the tumor growth, increased the percentage of CD86+ (35%) CD40+ (63%) and MHC class II+ (47%) and significantly increased the in vitro production of IFN-γ and decreased IL-10 by spleen cells co-culture. In addition we observed that the combination of DC vaccine with low dose 5-FU chemotherapy induced complete tumor regression in 75% of the treated animals.

Taken together our results indicate that low dose 5-FU plus DC vaccine can enhance the antitumor response and lead to complete tumor regression.

FAPESP 2009/18331-8; 2010/06013-9.